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Genomes and Genes
| Paolo PuccettiSummaryCountry: Italy Publications
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Publications
Effects of IL-12 and IL-23 on antigen-presenting cells at the interface between innate and adaptive immunityPaolo Puccetti
Department of Experimental Medicine, University of Perugia, Via del Giochetto, 06126 Perugia, Italy
Crit Rev Immunol 22:373-90. 2002..This review summarizes recent data on the actions of IL-12 and IL-23 on dendritic cells and macrophages at the interface between innate and adaptive immunity...
Generation of T cell regulatory activity by plasmacytoid dendritic cells and tryptophan catabolismPaolo Puccetti
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06126 Perugia, Italy
Blood Cells Mol Dis 40:101-5. 2008..Therefore, although pDCs do not express IDO-dependent tolerance constitutively, multiple ligands and cytokines will contribute to the expression of a tolerogenic phenotype by those cells...
IDO and regulatory T cells: a role for reverse signalling and non-canonical NF-kappaB activationPaolo Puccetti
Paolo Puccetti and Ursula Grohmann are at the Department of Experimental Medicine, Section of Pharmacology, University of Perugia, Perugia 06126, Italy
Nat Rev Immunol 7:817-23. 2007..This mechanism may also underlie the protective function of glucocorticoids in pathological conditions...
On watching the watchers: IDO and type I/II IFNPaolo Puccetti
Department of Experimental Medicine, University of Perugia, Perugia, Italy
Eur J Immunol 37:876-9. 2007..Such a bidirectional feedback loop could be part of an integrated response for preventing excessive inflammation and autoimmunity...
Cutting edge: silencing suppressor of cytokine signaling 3 expression in dendritic cells turns CD28-Ig from immune adjuvant to suppressantCiriana Orabona
Department of Experimental Medicine, University of Perugia, Italy
J Immunol 174:6582-6. 2005..Thus, in the absence of SOCS3, CD28-Ig becomes immunosuppressive and mimics the action of CTLA-4-Ig on tryptophan catabolism...
The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cellsFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 176:6752-61. 2006....
Tryptophan catabolism generates autoimmune-preventive regulatory T cellsFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Transpl Immunol 17:58-60. 2006..These cells are capable of effective control of diabetogenic T cells in vivo...
Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous diseaseLuigina Romani
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Nature 451:211-5. 2008..Yet, this condition can be reverted by reactivating the pathway downstream of the superoxide-dependent step...
Functional plasticity of dendritic cell subsets as mediated by CD40 versus B7 activationUrsula Grohmann
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
J Immunol 171:2581-7. 2003..Thus, environmental conditioning by T cell ligands may alter the default function of DC subsets to meet the needs of flexibility and redundancy...
IDO mediates TLR9-driven protection from experimental autoimmune diabetesFrancesca Fallarino
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
J Immunol 183:6303-12. 2009..Thus, our data suggest that the TLR9-IDO axis may represent a valuable target in the prevention/therapy of type 1 diabetes...
SOCS3 drives proteasomal degradation of indoleamine 2,3-dioxygenase (IDO) and antagonizes IDO-dependent tolerogenesisCiriana Orabona
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Proc Natl Acad Sci U S A 105:20828-33. 2008..In addition to identifying SOCS3 as a candidate signature for mouse DC subsets programmed to direct immunity, this study demonstrates that IDO undergoes regulatory proteolysis in response to immunogenic stimuli...
A crucial role for tryptophan catabolism at the host/Candida albicans interfaceSilvia Bozza
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
J Immunol 174:2910-8. 2005..The production of IFN-gamma may be squarely placed at this interface, where IDO activation probably exerts a fine control over fungal morphology as well as inflammatory and adaptive antifungal responses...
Immunity and tolerance to Aspergillus involve functionally distinct regulatory T cells and tryptophan catabolismClaudia Montagnoli
Department of Experimental Medicine and Biochemical Science, University of Perugia, Italy
J Immunol 176:1712-23. 2006..Thus, regulation is an essential component of the host response in infection and allergy to the fungus, and its manipulation may allow the pathogen to overcome host resistance and promote disease...
Immunosuppression via tryptophan catabolism: the role of kynurenine pathway enzymesMaria Laura Belladonna
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06126 Perugia, Italy
Transplantation 84:S17-20. 2007....
Thymosin alpha1: an endogenous regulator of inflammation, immunity, and toleranceLuigina Romani
Microbiology Section, Department of Experimental Medicine, and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy
Ann N Y Acad Sci 1112:326-38. 2007....
IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistanceTeresa Zelante
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Eur J Immunol 37:2695-706. 2007..As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi...
Ligand and cytokine dependence of the immunosuppressive pathway of tryptophan catabolism in plasmacytoid dendritic cellsFrancesca Fallarino
Department of Experimental Medicine, Section of Pharmacology, University of Perugia, 06126 Perugia, Italy
Int Immunol 17:1429-38. 2005..Therefore, although pDCs do not mediate IDO-dependent tolerance constitutively, multiple ligands and cytokines will contribute to the expression of a tolerogenic phenotype by pDCs in the mouse...
CD40 ligation prevents onset of tolerogenic properties in human dendritic cells treated with CTLA-4-IgCarmine Vacca
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy
Microbes Infect 7:1040-8. 2005..However, it is unable to induce suppressive properties in DC matured by CD40 engagement. Thus, CD40-driven events may physiologically set human DC free from restraint by regulatory cells expressing surface CTLA-4...
Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDOMaria L Belladonna
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy
J Immunol 177:130-7. 2006..The paracrine production of kynurenines might be one mechanism used by IDO-competent cells to convert DCs lacking functional IDO to a tolerogenic phenotype within an IFN-gamma-rich environment...
CTLA-4-Ig regulates tryptophan catabolism in vivoUrsula Grohmann
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Nat Immunol 3:1097-101. 2002..These data suggest that modulation of tryptophan catabolism is a means by which CTLA-4 functions in vivo and that CTLA-4 acts as a ligand for B7 receptor molecules that transduce intracellular signals...
Receptors and pathways in innate antifungal immunity: the implication for tolerance and immunity to fungiTeresa Zelante
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Adv Exp Med Biol 590:209-21. 2007
CD28 induces immunostimulatory signals in dendritic cells via CD80 and CD86Ciriana Orabona
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Nat Immunol 5:1134-42. 2004..Thus, different ligands of B7 can signal dendritic cells to express functionally distinct effector responses...
Cutting edge: Autocrine TGF-beta sustains default tolerogenesis by IDO-competent dendritic cellsMaria L Belladonna
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 181:5194-8. 2008..These data are the first to link TGF-beta signaling with IDO in controlling spontaneous tolerogenesis by DCs...
A defect in tryptophan catabolism impairs tolerance in nonobese diabetic miceUrsula Grohmann
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
J Exp Med 198:153-60. 2003..This is the first report of an experimental autoimmune disease in which defective tolerance is causally linked to impaired tryptophan catabolism...
Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagementFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 173:3748-54. 2004..These data prospect novel functions for both pDCs and the CD200-CD200R pair in the mouse. At the same time, these data underscore the possible unifying role of the IDO mechanism in immune tolerance...
Toward the identification of a tolerogenic signature in IDO-competent dendritic cellsCiriana Orabona
Section of Pharmacology, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06126 Perugia, Italy
Blood 107:2846-54. 2006..Overall, these studies reveal the occurrence of a simple and evolutionarily conserved code in the control of tolerance by an ancestral metabolic enzyme...
Modulation of tryptophan catabolism by regulatory T cellsFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Nat Immunol 4:1206-12. 2003..Thus, regulation of immunosuppressive tryptophan catabolism in dendritic cells might represent a major mechanism of action of T(R) cells...
Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infectionSilvia Bozza
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
J Immunol 180:4022-31. 2008..TIR8 may contribute toward fine-tuning the balance between protective immunity and immunopathology in infection...
Thymosin alpha1 activates dendritic cell tryptophan catabolism and establishes a regulatory environment for balance of inflammation and toleranceLuigina Romani
Dept of Experimental Medicine, Section of Microbiology, University of Perugia, Via del Giochetto, Perugia 06126, Italy
Blood 108:2265-74. 2006..Thus, instructive immunotherapy with Talpha1 targeting IDO-competent DCs could allow for a balanced control of inflammation and tolerance...
Enhanced tryptophan catabolism in the absence of the molecular adapter DAP12Ciriana Orabona
Department of Experimental Medicine, University of Perugia, Perugia, Italy
Eur J Immunol 35:3111-8. 2005..Increased resistance to experimental encephalomyelitis is observed in DAP12 knockin mice, which is dependent on IDO expression. Therefore, DAP12-related receptors act as negative regulators of IDO-mediated tolerance in vivo...
Tryptophan catabolism in nonobese diabetic miceUrsula Grohmann
Department of Experimental Medicine, University of Perugia, Italy
Adv Exp Med Biol 527:47-54. 2003..This finding correlates with a low expression of IDO activity, thus suggesting that poor expression of IDO by dendritic cells may play a role in the development of diabetes...
Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of RorcAntonella De Luca
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
J Immunol 179:5999-6008. 2007..This is the first study to show that the same tryptophan catabolites can foster dendritic cell-supported generation of Foxp3(+) cells and mediate, at the same time, inhibition of RORgammat-expressing T cells...
Indoleamine 2,3-dioxygenase (IDO) in inflammation and allergy to AspergillusLuigina Romani
Department of Experimental Medicine and Biochemical Sciences and Fondazione, Istituto di Ricovero e Cura per le Biotecnologie Trapiantologiche, Perugia, Italy
Med Mycol 47:S154-61. 2009....
Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cellsMaria T Pallotta
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Nat Immunol 12:870-8. 2011..Thus, IDO has a tonic, nonenzymic function that contributes to TGF-?-driven tolerance in noninflammatory contexts...
CTLA-4-Ig activates forkhead transcription factors and protects dendritic cells from oxidative stress in nonobese diabetic miceFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia 06126, Italy
J Exp Med 200:1051-62. 2004....
T cell apoptosis by kynureninesFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Italy
Adv Exp Med Biol 527:183-90. 2003..These data may represent the first experimental evidence for the involvement of tryptophan catabolism in the regulation of T cell apoptosis and maintenance of peripheral T cell tolerance...
Reverse signaling through GITR ligand enables dexamethasone to activate IDO in allergyUrsula Grohmann
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, 06126 Perugia, Italy
Nat Med 13:579-86. 2007..Induction of IDO could be an important mechanism underlying the anti-inflammatory action of corticosteroids...
IL-17 and therapeutic kynurenines in pathogenic inflammation to fungiLuigina Romani
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
J Immunol 180:5157-62. 2008..Recent data support a view in which IL-23/IL-17 antagonistic strategies, including the administration of synthetic kynurenines, could represent a new means of harnessing progressive or potentially harmful inflammation...
Controlling pathogenic inflammation to fungiLuigina Romani
University of Perugia, Department of Experimental Medicine and Biochemical Sciences, Via del Giochetto, 06122 Perugia, Italy
Expert Rev Anti Infect Ther 5:1007-17. 2007....
Xenograft of microencapsulated sertoli cells reverses T1DM in NOD mice by inducing neogenesis of beta-cellsGiovanni Luca
Department of Experimental Medicine, University of Perugia, Perugia, Italy
Transplantation 90:1352-7. 2010....
IL-23 neutralization protects mice from Gram-negative endotoxic shockMaria Laura Belladonna
Department of Experimental Medicine and Biochemical Sciences, Section of Pharmacology, University of Perugia, Via del Giochetto, Perugia 06126, Italy
Cytokine 34:161-9. 2006..aeruginosa-challenged mice was associated with a dramatic decrease in circulating levels of the pathogenetic cytokines, TNF-alpha and IFN-gamma. Hence, IL-23 may represent a new therapeutic target in Gram-negative endotoxic shock...
TGF-beta and kynurenines as the key to infectious toleranceMaria L Belladonna
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06126, Italy
Trends Mol Med 15:41-9. 2009..Current molecular insights suggest a synergistic potential for TGF-beta and IDO in physiologically or therapeutically opposing human pathologies sustained by over-reacting immune responses...
CD40 ligand and CTLA-4 are reciprocally regulated in the Th1 cell proliferative response sustained by CD8(+) dendritic cellsFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 169:1182-8. 2002..In addition, they suggest that reciprocal regulation of CD40 ligand and CTLA-4 expression occurs in Th1 cells exposed to CD8(+) DCs...
Metabotropic glutamate receptor-4 modulates adaptive immunity and restrains neuroinflammationFrancesca Fallarino
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Nat Med 16:897-902. 2010..The high amounts of glutamate in neuroinflammation might reflect a counterregulatory mechanism that is protective in nature and might be harnessed therapeutically for restricting immunopathology in multiple sclerosis...
IL-23 and IL-12 have overlapping, but distinct, effects on murine dendritic cellsMaria Laura Belladonna
Department of Experimental Medicine, University of Perugia, Perugia, Italy
J Immunol 168:5448-54. 2002..In addition, the in vitro effects of IL-23-Ig did not appear to require IL-12Rbeta2 or to be mediated by the production of IL-12. These data may establish IL-23 as a novel cytokine with major effects on APC...
Indoleamine 2,3-dioxygenase in infection: the paradox of an evasive strategy that benefits the hostTeresa Zelante
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Microbes Infect 11:133-41. 2009..This review deals with recent findings that could gain IDO a reputation of Jack-of-all-trades in mammalian host/microbe interactions...
Immune regulation and tolerance to fungi in the lungs and skinLuigina Romani
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
Chem Immunol Allergy 94:124-37. 2008..IDO and tryptophan metabolites may prove to be potent regulators capable of taming overzealous or heightened inflammatory host responses...
Tolerance, DCs and tryptophan: much ado about IDOUrsula Grohmann
Department of Experimental Medicine, Via del Giochetto, University of Perugia, 06126 Perugia, Italy
Trends Immunol 24:242-8. 2003
Therapy of experimental type 1 diabetes by isolated Sertoli cell xenografts aloneFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia 06126, Italy
J Exp Med 206:2511-26. 2009....
CTLA-4, T helper lymphocytes and dendritic cells: an internal perspective of T-cell homeostasisUrsula Grohmann
Department of Experimental Medicine, Via del Giochetto, University of Perugia, 06126 Perugia, Italy
Trends Mol Med 9:133-5. 2003....
Protective tolerance to fungi: the role of IL-10 and tryptophan catabolismLuigina Romani
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06126 Perugia, Italy
Trends Microbiol 14:183-9. 2006..T-reg cells, however, might also represent an additional mechanistic level at which host responses are subverted by fungi...
The exploitation of distinct recognition receptors in dendritic cells determines the full range of host immune relationships with Candida albicansLuigina Romani
Department of Experimental Medicine and Biochemical Science, University of Perugia, 06122 Perugia, Italy
Int Immunol 16:149-61. 2004..albicans is shared by the organism and DC, with implications for fungal virulence, immunity and vaccine development...
Functional expression of indoleamine 2,3-dioxygenase by murine CD8 alpha(+) dendritic cellsFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia 06122, Italy
Int Immunol 14:65-8. 2002..Therefore, in the mouse, CD8 alpha(+) DC may be unique APC capable of fully expressing the IDO mechanism functionally...
Proteasomal Degradation of Indoleamine 2,3-Dioxygenase in CD8 Dendritic Cells is Mediated by Suppressor of Cytokine Signaling 3 (SOCS3)Maria T Pallotta
Department of Experimental Medicine, University of Perugia, 06126 Perugia, Italy
Int J Tryptophan Res 3:91-7. 2010..These studies support the finding that IDO is regulated by proteasomal degradation in response to immunogenic and inflammatory stimuli...
Adaptation of Candida albicans to the host environment: the role of morphogenesis in virulence and survival in mammalian hostsLuigina Romani
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, 06122 Perugia, Italy
Curr Opin Microbiol 6:338-43. 2003..The fitness of the fungus in vivo probably reflects its adaptation to the variety of microenvironments in which this opportunist must survive...
Toll-like receptor 9-mediated induction of the immunosuppressive pathway of tryptophan catabolismFrancesca Fallarino
Department of Experimental Medicine, University of Perugia, Perugia, Italy
Eur J Immunol 36:8-11. 2006..At the same time, these studies may offer novel opportunities for use of CpG-ODN as immunosuppressive agents and may also lead to an improved understanding of the cellular events mediated by Toll-like receptor 9 signaling...
Sensing of mammalian IL-17A regulates fungal adaptation and virulenceTeresa Zelante
Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia 06122, Italy
Nat Commun 3:683. 2012..This might exemplify a mechanism whereby fungi have evolved a means of sensing host immunity to ensure their own persistence in an immunologically dynamic environment...
Fungi, dendritic cells and receptors: a host perspective of fungal virulenceLuigina Romani
Dept of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, Italy
Trends Microbiol 10:508-14. 2002....
